Role of magnetic resonance spectroscopy in cerebral glutathione quantification for youth mental health: A systematic review

Abstract

Aim Oxidative stress is strongly implicated in many psychiatric disorders, which has resulted in the development of new interventions to attempt to perturb this pathology. A great deal of attention has been paid to glutathione, which is the brain's dominant antioxidant and plays a fundamental role in removing free radicals and other reactive oxygen species. Measurement of glutathione concentration in the brain in vivo can provide information on redox status and potential for oxidative stress to develop. Glutathione might also represent a marker to assess treatment response. Methods This paper systematically reviews studies that assess glutathione concentration (measured using magnetic resonance spectroscopy) in various mental health conditions. Results There is limited evidence showing altered brain glutathione concentration in mental disorders; the best evidence suggests glutathione is decreased in depression, but is not altered in bipolar disorder. The review then outlines the various methodological options for acquiring glutathione data using spectroscopy. Conclusions Analysis of the minimum effect size measurable in existing studies indicates that increased number of participants is required to measure subtle but possibly important differences and move the field forward.

In Vivo Brain GSH: MRS Methods and Clinical Applications

“…Alternative approaches were also introduced to overcome metabolite overlap, including more advanced shimming technologies [ 23 ], spreading out the signal into a second frequency dimension (i.e., 2D MRS), or the use of higher B0, as the relative width of multiplets (in ppm) is inversely proportional to the field strength [ 37 ]. Given the pivotal role of GSH in the human brain, an increasing number of studies have been performed with sophisticated MRS techniques to reliably assess GSH concentration [ 22 , 38 ]. Although the methods reported in the literature are highly heterogeneous (i.e., different acquisition techniques, different voxel size and placement, and different post-processing), we provide a detailed description of the current methods for GSH measurement within the next sections, differentiating unedited and edited spectrum techniques.…”

Is There a Glutathione Centered Redox Dysregulation Subtype of Schizophrenia?

“…In depression, this early-life reduction in GSH levels [96,97] appears to normalise later (15.7% increase, 1 year after first-episode depression [98]), likely explaining the higher than expected levels in later life [99]. At present, the relative influence of lifestyle factors on intracortical GSH in schizophrenia is unknown.…”

Is There a Glutathione Centered Redox Dysregulation Subtype of Schizophrenia?

“…For example, in youth with mood disorders [ 91 ], apparent intracortical GSH-deficits are mostly explained by lifestyle factors (alcohol or smoking) [ 89 , 92 , 93 ]. In depression, this early-life reduction in GSH levels [ 94 , 95 ] appears to normalise later (15.7% increase, 1 year after first-episode depression [ 96 ]), likely explaining the higher than expected levels in later life [ 97 ]. At present, the relative influence of lifestyle factors on intracortical GSH in schizophrenia is unknown.…”